Roles of synaptic cell adhesion molecules in the neuromodulatory systems

Jennifer Li; Yuka Imamura Kawasawa; Motokazu Uchigashima; Kensuke Futai

doi:10.1016/j.mocell.2026.100340

Roles of synaptic cell adhesion molecules in the neuromodulatory systems

Mol Cells. 2026 May;49(5):100340. doi: 10.1016/j.mocell.2026.100340. Epub 2026 Feb 27.

Authors

Jennifer Li¹, Yuka Imamura Kawasawa², Motokazu Uchigashima³, Kensuke Futai⁴

Affiliations

¹ Department of Neurobiology, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, 366 Plantation Street, Worcester, MA 01605, USA.
² Department of Neuroscience and Experimental Therapeutics, Penn State College of Medicine, 500 University Dr., Hershey, PA 17033, USA.
³ Department of Cellular Neuropathology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan; International Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo, Tokyo 113-0033, Japan. Electronic address: uchigashima@bri.niigata-u.ac.jp.
⁴ Department of Neurobiology, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, 366 Plantation Street, Worcester, MA 01605, USA. Electronic address: Kensuke.Futai@umassmed.edu.

Abstract

Synaptic cell-adhesion molecules (CAMs), also known as trans-synaptic adhesion molecules, are essential for synapse development and maintenance by physically linking presynaptic terminals to postsynaptic structures. Extensive research has established that synaptic CAMs are critical for the formation and function of various synapse types, particularly glutamatergic and GABAergic synapses. However, their roles within modulatory systems, such as dopaminergic (DA) and serotonergic (5-HT) circuits, which utilize both synaptic and non-synaptic (volume) transmission, remain poorly understood. In this mini review, we analyzed published single-cell transcriptomic datasets of DA and 5-HT neurons to characterize presynaptic CAM expression in these systems. We further summarized current knowledge regarding the contribution of presynaptic CAMs to DA and 5-HT function and discuss how postsynaptic CAM-mediated mechanisms shape dopaminergic synaptic architecture.

Keywords: Autism spectrum disorder; Dopamine; Neurodevelopmental disorders; Serotonin; Trans-synaptic adhesion molecules.

Publication types

Review

MeSH terms

Animals
Cell Adhesion Molecules* / metabolism
Humans
Neurotransmitter Agents* / metabolism
Synapses* / metabolism
Synaptic Transmission

Substances

Cell Adhesion Molecules
Neurotransmitter Agents